Blastocyst transfer is commonly, but erroneously, believed to result in higher live birth rates than transfer of embryos at an earlier stage. In fact the main advantage of blastocyst transfer lies not in providing superior live birth rates but in achieving acceptable take home baby rate with transfer of just a single embryo. Single embryo transfer, of course, eliminates all high order multiple births and fraternal twins (The Dilemma of Twins). Transfer of two blastocysts, however, leads to a fraternal twin rate in excess of 50%. In our program, patients in the good prognosis group can choose between transfer of 2 embryos on day 3 or transfer of a single blastocyst on day 5 or 6.
A perfect 8-cell embryo 3 days after retrieval
Traditionally embryos have been transferred into the uterus 2-3 days after egg retrieval whereas blastocyst transfer usually takes place 5-6 days after retrieval. The theoretical rationale for growing embryos to the blastocyst stage is that, with longer time in culture, it is easier to select the single best embryo out of a large number of fertilized eggs than it is at an earlier stage. For successful implantation to occur an embryo must become a blastocyst. In natural conception an embryo reaches the uterine cavity 4-5 days after ovulation when it is at the blastocyst stage. In the laboratory embryos may take a day longer to become a blastocyst hence the transfer on day 5 or 6. Thus embryo selection and physiology both appear to favor blastocyst transfer.
Blastocyst with an inner cell mass which gives rise to the fetus
As usual though, the reality of human IVF is a bit more complex. Embryo selection is important in women who have a large number of normally fertilized eggs, for instance more than 12, and in whom it is advisable to limit the number of embryos transferred to just one. A good example may be a young woman with good ovarian reserve who has a malformed and small uterus for whom carrying twins increases the risk of premature delivery. This situation occurs primarily in women under the age of 35 years undergoing IVF with their own eggs and in older patients using donor eggs. Many women above the age of 35 years have a smaller number of fertilized eggs and may wish to compensate for the lower viability of their embryos by transferring more than one at a time (What Is Age Factor? How Do We Test for Ovarian Reserve?).
In a program such as ours, where most patients are above the age of 35 years and reduced ovarian reserve is common, there are relatively few ideal candidates for blastocyst transfer. Couples with severe male factor often have low fertilization and embryo development rates so they seldom benefit from extended culture to the blastocyst stage.
Extended culture to the blastocyst stage has been associated with increased risk of identical (monozygotic) twins who face much higher risks during pregnancy than fraternal twins. It has also been suggested that prolonged exposure to laboratory conditions might increase the risk of so=called imprinting genetic disorders.
Without careful selection of patients for transfer on day 5 or 6, a significant number of couples (5-10%) may end up with no blastocysts suitable for transfer. Yet some of these patients can conceive with a day 2-3 transfer. Despite major advances, laboratory conditions remain less than ideal and some embryos may develop only in the more physiological milieu of the reproductive tract.
Finally, extended culture to the blastocyst stage reduces the number of embryos available for freezing. In our experience and the experience of others, transfer of frozen-thawed embryos adds significantly to the overall live birth rate per retrieval (Our Results). In some fresh cycles uterine receptivity towards embryo implantation is compromised and better receptivity can be achieved in controlled frozen embryo transfer cycles (What is Involved in Embryo Freezing?). Therefore, maximizing the number of embryos available for freezing is a key element of our overall treatment strategy.
In summary, single blastocyst transfer has an important role in the practice of assisted reproduction, particularly in the care of patients who should avoid twins for best pregnancy outcome. However, most of our patients elect to have embryo transfer at an earlier stage. This practice is in agreement with the national trends: in 2006 67.8% of all transfers of fresh non-donor eggs occurred on days 2-3 and 28.6% took place on days 5-6. Fortunately, the final decision of when it is best to perform the transfer in a given cycle can be usually made on short notice once it is known how many embryos are developing normally.